Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Dec 2002; 162(4): 1573–1581.
PMCID: PMC1462392

Candida albicans Mds3p, a conserved regulator of pH responses and virulence identified through insertional mutagenesis.


Candida albicans is a commensal fungus that causes diverse infections after antibiotic use or immune debilitation. Gene discovery has been limited because the organism is an asexual diploid. We have developed a strategy that yields random homozygous insertion mutants. The strategy has permitted identification of several prospective essential genes. Many of these genes are homologous to nonessential Saccharomyces cerevisiae genes, and some have no S. cerevisiae homolog. These findings may expand the range of antifungal drug targets. We have also identified new genes required for pH-dependent filamentation, a trait previously associated with virulence. One newly identified gene, MDS3, is required for expression in alkaline media of two filamentation-associated genes, HWP1 and ECE1, but is not required for expression of other pH-response genes. In S. cerevisiae, the two MDS3 homologs are required for growth in alkaline media, thus arguing that Mds3p function in adaptation to external pH changes is conserved. Epistasis tests show that Mds3p contributes to virulence and alkaline pH responses independently of the well-characterized Rim101p pH-response pathway.

Full Text

The Full Text of this article is available as a PDF (255K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Davis D, Edwards JE, Jr, Mitchell AP, Ibrahim AS. Candida albicans RIM101 pH response pathway is required for host-pathogen interactions. Infect Immun. 2000 Oct;68(10):5953–5959. [PMC free article] [PubMed]
  • Davis D, Wilson RB, Mitchell AP. RIM101-dependent and-independent pathways govern pH responses in Candida albicans. Mol Cell Biol. 2000 Feb;20(3):971–978. [PMC free article] [PubMed]
  • Denison SH. pH regulation of gene expression in fungi. Fungal Genet Biol. 2000 Mar;29(2):61–71. [PubMed]
  • Douglas CM, D'Ippolito JA, Shei GJ, Meinz M, Onishi J, Marrinan JA, Li W, Abruzzo GK, Flattery A, Bartizal K, et al. Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-D-glucan synthase inhibitors. Antimicrob Agents Chemother. 1997 Nov;41(11):2471–2479. [PMC free article] [PubMed]
  • El Barkani A, Kurzai O, Fonzi WA, Ramon A, Porta A, Frosch M, Mühlschlegel FA. Dominant active alleles of RIM101 (PRR2) bypass the pH restriction on filamentation of Candida albicans. Mol Cell Biol. 2000 Jul;20(13):4635–4647. [PMC free article] [PubMed]
  • Ellepola AN, Samaranayake LP. Inhalational and topical steroids, and oral candidosis: a mini review. Oral Dis. 2001 Jul;7(4):211–216. [PubMed]
  • Enloe B, Diamond A, Mitchell AP. A single-transformation gene function test in diploid Candida albicans. J Bacteriol. 2000 Oct;182(20):5730–5736. [PMC free article] [PubMed]
  • Epstein CB, Cross FR. Genes that can bypass the CLN requirement for Saccharomyces cerevisiae cell cycle START. Mol Cell Biol. 1994 Mar;14(3):2041–2047. [PMC free article] [PubMed]
  • Farah CS, Ashman RB, Challacombe SJ. Oral candidosis. Clin Dermatol. 2000 Sep-Oct;18(5):553–562. [PubMed]
  • Feng Q, Summers E, Guo B, Fink G. Ras signaling is required for serum-induced hyphal differentiation in Candida albicans. J Bacteriol. 1999 Oct;181(20):6339–6346. [PMC free article] [PubMed]
  • Fidel PL, Jr, Sobel JD. Immunopathogenesis of recurrent vulvovaginal candidiasis. Clin Microbiol Rev. 1996 Jul;9(3):335–348. [PMC free article] [PubMed]
  • Fonzi WA, Irwin MY. Isogenic strain construction and gene mapping in Candida albicans. Genetics. 1993 Jul;134(3):717–728. [PMC free article] [PubMed]
  • Fu Y, Rieg G, Fonzi WA, Belanger PH, Edwards JE, Jr, Filler SG. Expression of the Candida albicans gene ALS1 in Saccharomyces cerevisiae induces adherence to endothelial and epithelial cells. Infect Immun. 1998 Apr;66(4):1783–1786. [PMC free article] [PubMed]
  • Futcher B. Cyclins and the wiring of the yeast cell cycle. Yeast. 1996 Dec;12(16):1635–1646. [PubMed]
  • Lamb TM, Xu W, Diamond A, Mitchell AP. Alkaline response genes of Saccharomyces cerevisiae and their relationship to the RIM101 pathway. J Biol Chem. 2001 Jan 19;276(3):1850–1856. [PubMed]
  • Lane S, Zhou S, Pan T, Dai Q, Liu H. The basic helix-loop-helix transcription factor Cph2 regulates hyphal development in Candida albicans partly via TEC1. Mol Cell Biol. 2001 Oct;21(19):6418–6428. [PMC free article] [PubMed]
  • Lee KL, Buckley HR, Campbell CC. An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida Albicans. Sabouraudia. 1975 Jul;13(2):148–153. [PubMed]
  • Asleson CM, Bensen ES, Gale CA, Melms AS, Kurischko C, Berman J. Candida albicans INT1-induced filamentation in Saccharomyces cerevisiae depends on Sla2p. Mol Cell Biol. 2001 Feb;21(4):1272–1284. [PMC free article] [PubMed]
  • Li W, Mitchell AP. Proteolytic activation of Rim1p, a positive regulator of yeast sporulation and invasive growth. Genetics. 1997 Jan;145(1):63–73. [PMC free article] [PubMed]
  • Liu H, Köhler J, Fink GR. Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science. 1994 Dec 9;266(5191):1723–1726. [PubMed]
  • Mio T, Adachi-Shimizu M, Tachibana Y, Tabuchi H, Inoue SB, Yabe T, Yamada-Okabe T, Arisawa M, Watanabe T, Yamada-Okabe H. Cloning of the Candida albicans homolog of Saccharomyces cerevisiae GSC1/FKS1 and its involvement in beta-1,3-glucan synthesis. J Bacteriol. 1997 Jul;179(13):4096–4105. [PMC free article] [PubMed]
  • Natarajan K, Datta A. Molecular cloning and analysis of the NAG1 cDNA coding for glucosamine-6-phosphate deaminase from Candida albicans. J Biol Chem. 1993 May 5;268(13):9206–9214. [PubMed]
  • Navarro-García F, Sánchez M, Nombela C, Pla J. Virulence genes in the pathogenic yeast Candida albicans. FEMS Microbiol Rev. 2001 Apr;25(2):245–268. [PubMed]
  • Caponigro G, Abedi MR, Hurlburt AP, Maxfield A, Judd W, Kamb A. Transdominant genetic analysis of a growth control pathway. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7508–7513. [PMC free article] [PubMed]
  • Patterson JE. Epidemiology of fungal infections in solid organ transplant patients. Transpl Infect Dis. 1999 Dec;1(4):229–236. [PubMed]
  • Cognetti David, Davis Dana, Sturtevant Joy. The Candida albicans 14-3-3 gene, BMH1, is essential for growth. Yeast. 2002 Jan 15;19(1):55–67. [PubMed]
  • Petter R, Chang YC, Kwon-Chung KJ. A gene homologous to Saccharomyces cerevisiae SNF1 appears to be essential for the viability of Candida albicans. Infect Immun. 1997 Dec;65(12):4909–4917. [PMC free article] [PubMed]
  • Tzung KW, Williams RM, Scherer S, Federspiel N, Jones T, Hansen N, Bivolarevic V, Huizar L, Komp C, Surzycki R, et al. Genomic evidence for a complete sexual cycle in Candida albicans. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3249–3253. [PMC free article] [PubMed]
  • Pla J, Gil C, Monteoliva L, Navarro-García F, Sánchez M, Nombela C. Understanding Candida albicans at the molecular level. Yeast. 1996 Dec;12(16):1677–1702. [PubMed]
  • Whiteway M, Dignard D, Thomas DY. Dominant negative selection of heterologous genes: isolation of Candida albicans genes that interfere with Saccharomyces cerevisiae mating factor-induced cell cycle arrest. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9410–9414. [PMC free article] [PubMed]
  • Porta A, Ramon AM, Fonzi WA. PRR1, a homolog of Aspergillus nidulans palF, controls pH-dependent gene expression and filamentation in Candida albicans. J Bacteriol. 1999 Dec;181(24):7516–7523. [PMC free article] [PubMed]
  • Wijnen H, Futcher B. Genetic analysis of the shared role of CLN3 and BCK2 at the G(1)-S transition in Saccharomyces cerevisiae. Genetics. 1999 Nov;153(3):1131–1143. [PMC free article] [PubMed]
  • Wilson RB, Davis D, Mitchell AP. Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol. 1999 Mar;181(6):1868–1874. [PMC free article] [PubMed]
  • Rojo E, Gillmor CS, Kovaleva V, Somerville CR, Raikhel NV. VACUOLELESS1 is an essential gene required for vacuole formation and morphogenesis in Arabidopsis. Dev Cell. 2001 Aug;1(2):303–310. [PubMed]
  • Wilson RB, Davis D, Enloe BM, Mitchell AP. A recyclable Candida albicans URA3 cassette for PCR product-directed gene disruptions. Yeast. 2000 Jan 15;16(1):65–70. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Taxonomy
    Related taxonomy entry
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...